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Histone demethylase

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https://www.readbyqxmd.com/read/29142071/chromatin-histone-modifications-and-rigidity-affect-nuclear-morphology-independent-of-lamins
#1
Andrew D Stephens, Patrick Z Liu, Edward J Banigan, Luay M Almassalha, Vadim Backman, Stephen A Adam, Robert D Goldman, John F Marko
Nuclear shape and architecture influence gene localization, mechanotransduction, transcription, and cell function. Abnormal nuclear morphology and protrusions termed "blebs" are diagnostic markers for many human afflictions including heart disease, aging, progeria, and cancer. Nuclear blebs are associated with both lamin and chromatin alterations. A number of prior studies suggest that lamins dictate nuclear morphology, but the contributions of altered chromatin compaction remain unclear. We show that chromatin histone modification state dictates nuclear rigidity, and modulating it is sufficient to both induce and suppress nuclear blebs...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29140109/host-methyltransferases-and-demethylases-potential-new-epigenetic-targets-for-hiv-cure-strategies-and-beyond
#2
Daniela Boehm, Melanie Ott
A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#3
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136510/genomic-subtypes-of-non-invasive-bladder-cancer-with-distinct-metabolic-profile-and-female-gender-bias-in-kdm6a-mutation-frequency
#4
Carolyn D Hurst, Olivia Alder, Fiona M Platt, Alastair Droop, Lucy F Stead, Julie E Burns, George J Burghel, Sunjay Jain, Leszek J Klimczak, Helen Lindsay, Jo-An Roulson, Claire F Taylor, Helene Thygesen, Angus J Cameron, Anne J Ridley, Helen R Mott, Dmitry A Gordenin, Margaret A Knowles
Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29126261/heme-promotes-transcriptional-and-demethylase-activities-of-gis1-a-member-of-the-histone-demethylase-jmjd2-kdm4-family
#5
Sneha Lal, Jonathan M Comer, Purna C Konduri, Ajit Shah, Tianyuan Wang, Anthony Lewis, Grant Shoffner, Feng Guo, Li Zhang
The yeast Gis1 protein is a transcriptional regulator belonging to the JMJD2/KDM4 subfamily of demethylases that contain a JmjC domain, which are highly conserved from yeast to humans. They have important functions in histone methylation, cellular signaling and tumorigenesis. Besides serving as a cofactor in many proteins, heme is known to directly regulate the activities of proteins ranging from transcriptional regulators to potassium channels. Here, we report a novel mechanism governing heme regulation of Gis1 transcriptional and histone demethylase activities...
November 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29113308/kdm4a-as-a-prognostic-marker-of-oral-squamous-cell-carcinoma-evidence-from-tissue-microarray-studies-in-a-multicenter-cohort
#6
Xin Jin, Hao Xu, Xingyu Wu, Taiwen Li, Jing Li, Yu Zhou, Hongxia Dan, Lu Jiang, Xin Zeng, Ping Ji, Qianming Chen
Purpose: Previous studies have identified histone demethylase KDM4A to be a key epigenetic priming factor for the invasive squamous cell carcinoma growth and metastasis. The purpose of this study was to examine KDM4A as an independent prognostic marker in oral squamous cell carcinoma, using multicenter tissue microarrays. Results: The expression of KDM4A was significantly correlated with lymph node metastasis and TNM stage. KDM4A overexpression was associated with poor overall survival, and it was found to be a statistically significant independent predictor of all-cause mortality...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111428/kdm6-and-kdm4-histone-lysine-demethylases-emerge-as-molecular-therapeutic-targets-in-human-acute-myeloid-leukemia
#7
Liberalis Debraj Boila, Shankha Subhra Chatterjee, Debasis Banerjee, Amitava Sengupta
Acute myeloid leukemia (AML) remains an aggressive hematopoietic malignancy caused by proliferation of immature myeloid cells, which is frequently characterized by perturbations in chromatin modifying enzymes. Emerging evidences indicate that histone demethylases play instructive role in tumorigenesis. However, due to the complexity of this enormous family of histone-modifying enzymes, substrate redundancy and context-specific roles, the contribution of each member remains ambiguous and targeting them remains challenging...
October 27, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29108280/trimethylation-of-h3k27-during-human-cerebellar-development-in-relation-to-medulloblastoma
#8
Shahryar E Mir, Michiel Smits, Dennis Biesmans, Machteld Julsing, Marianna Bugiani, Eleonora Aronica, Gertjan J L Kaspers, Jacqueline Cloos, Thomas Würdinger, Esther Hulleman
Medulloblastoma (MB), the most common malignant childhood brain tumor, encompasses a collection of four clinically and molecularly distinct tumor subgroups, i.e. WNT, SHH, Group 3 and Group 4. These tumors are believed to originate from precursor cells during cerebellar development. Although the exact etiology of these brain tumors is not yet known, histone modifications are increasingly recognized as key events during cerebellum development and MB tumorigenesis. Recent studies show that key components involved in post-translational modifications of histone H3 lysine 27 (H3K27) are commonly deregulated in MB...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104258/epigenetic-regulatory-mechanisms-induced-by-resveratrol
#9
REVIEW
Guilherme Felipe Santos Fernandes, Gabriel Dalio Bernardes Silva, Aline Renata Pavan, Diego Eidy Chiba, Chung Man Chin, Jean Leandro Dos Santos
Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT), histone deacetylase (HDAC) and lysine-specific demethylase-1 (LSD1)...
November 1, 2017: Nutrients
https://www.readbyqxmd.com/read/29101321/contribution-of-epigenetic-landscapes-and-transcription-factors-to-x-chromosome-reactivation-in-the-inner-cell-mass
#10
Maud Borensztein, Ikuhiro Okamoto, Laurène Syx, Guillaume Guilbaud, Christel Picard, Katia Ancelin, Rafael Galupa, Patricia Diabangouaya, Nicolas Servant, Emmanuel Barillot, Azim Surani, Mitinori Saitou, Chong-Jian Chen, Konstantinos Anastassiadis, Edith Heard
X-chromosome inactivation is established during early development. In mice, transcriptional repression of the paternal X-chromosome (Xp) and enrichment in epigenetic marks such as H3K27me3 is achieved by the early blastocyst stage. X-chromosome inactivation is then reversed in the inner cell mass. The mechanisms underlying Xp reactivation remain enigmatic. Using in vivo single-cell approaches (allele-specific RNAseq, nascent RNA-fluorescent in situ hybridization and immunofluorescence), we show here that different genes are reactivated at different stages, with more slowly reactivated genes tending to be enriched in H3meK27...
November 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/29099285/critical-roles-of-protein-methyltransferases-and-demethylases-in-the-regulation-of-embryonic-stem-cell-fate
#11
Theodore Vougiouklakis, Yusuke Nakamura, Vassiliki Saloura
Accumulating evidence has recently shown that protein methyltransferases and demethylases are crucial regulators in either maintaining pluripotent states or inducing differentiation of embryonic stem cells. These enzymes control pluripotent signatures by mediating activation or repression of histone marks, or through direct methylation of non-histone proteins. Importantly, chromatin modifiers can influence the fate of many differentiation-related genes by loosening chromatin and allowing for transcriptional activation of lineage-specific genes...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099276/setdb2-and-riox2-are-differentially-expressed-among-renal-cell-tumor-subtypes-associating-with-prognosis-and-metastization
#12
Maria João Ferreira, Ana Sílvia Pires-Luís, Márcia Vieira-Coimbra, Pedro Costa-Pinheiro, Luís Antunes, Paula C Dias, Francisco Lobo, Jorge Oliveira, Céline S Gonçalves, Bruno M Costa, Rui Henrique, Carmen Jerónimo
Increasing detection of small renal masses by imaging techniques entails the need for accurate discrimination between benign and malignant renal cell tumors (RCTs) as well as among malignant RCTs, owing to differential risk of progression through metastization. Although histone methylation has been implicated in renal tumorigenesis, its potential as biomarker for renal cell carcinoma (RCC) progression remains largely unexplored. Thus, we aimed to characterize the differential expression of histone methyltransferases (HMTs) and histone demethylases (HDMs) in RCTs to assess their potential as metastasis biomarkers...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29097205/characterization-of-human-alkb-homolog-1-produced-in-mammalian-cells-and-demonstration-of-mitochondrial-dysfunction-in-alkbh1-deficient-cells
#13
Tina A Müller, Sarah L Struble, Katheryn Meek, Robert P Hausinger
Alkbh1 is a mammalian homolog of the Escherichia coli DNA repair enzyme AlkB, an Fe(II) and 2-oxoglutarate dependent dioxygenase that removes alkyl lesions from DNA bases. The human homolog ALKBH1 has been associated with six different enzymatic activities including DNA or tRNA hydroxylation, cleavage at abasic (AP) sites in DNA, as well as demethylation of histones. The reported cellular roles of this protein reflect the diverse enzymatic activities and include direct DNA repair, tRNA modification, and histone modification...
October 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29082591/the-involvement-of-histone-methylation-in-osteoblastic-differentiation-of-human-periosteum-derived-cells-cultured-in-vitro-under-hypoxic-conditions
#14
Dae-Kwan Yoon, Ji-Sung Park, Gyu-Jin Rho, Hyeon-Jeong Lee, Iel-Yong Sung, Jang-Ho Son, Bong-Wook Park, Young-Hoon Kang, Sung-Hoon Byun, Sun-Chul Hwang, Dong Kyun Woo, Yeong-Cheol Cho, June-Ho Byun
Although oxygen concentrations affect the growth and function of mesenchymal stem cells (MSCs), the impact of hypoxia on osteoblastic differentiation is not understood. Likewise, the effect of hypoxia-induced epigenetic changes on osteoblastic differentiation of MSCs is unknown. The aim of this study was to examine the in vitro hypoxic response of human periosteum-derived cells (hPDCs). Hypoxia resulted in greater proliferation of hPDCs as compared with those cultured in normoxia. Further, hypoxic conditions yielded decreased expression of apoptosis- and senescence-associated genes by hPDCs...
October 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29077881/interplay-among-h3k9-editing-enzymes-suv39h1-jmjd2c-and-src-1-drives-p66shc-transcription-and-vascular-oxidative-stress-in-obesity
#15
Sarah Costantino, Francesco Paneni, Agostino Virdis, Shafaat Hussain, Shafeeq Ahmed Mohammed, Giuliana Capretti, Alexander Akhmedov, Kevin Dalgaard, Sergio Chiandotto, J Andrew Pospisilik, Thomas Jenuwein, Marco Giorgio, Massimo Volpe, Stefano Taddei, Thomas F Lüscher, Francesco Cosentino
Aims: Accumulation of reactive oxygen species (ROS) promotes vascular disease in obesity, but the underlying molecular mechanisms remain poorly understood. The adaptor p66Shc is emerging as a key molecule responsible for ROS generation and vascular damage. This study investigates whether epigenetic regulation of p66Shc contributes to obesity-related vascular disease. Methods and results: ROS-driven endothelial dysfunction was observed in visceral fat arteries (VFAs) isolated from obese subjects when compared with normal weight controls...
October 25, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29076964/lysine-methylation-signaling-in-pancreatic-cancer
#16
Gaël S Roth, Alexandre G Casanova, Nathanaël Lemonnier, Nicolas Reynoird
PURPOSE OF REVIEW: Despite better knowledge of its genetic basis, pancreatic cancer is still highly lethal with very few therapeutic options. In this review, we discuss the potential impact of epigenetic therapies, focusing on lysine methylation signaling and its implication in pancreatic cancer. RECENT FINDINGS: Protein lysine methylation, a key mechanism of posttranslational modifications of histone proteins, has emerged as a major cell signaling mechanism regulating physiologic and pathologic processes including cancer...
October 25, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29075615/pharmacologic-targeting-of-chromatin-modulators-as-therapeutics-of-acute-myeloid-leukemia
#17
REVIEW
Rui Lu, Gang Greg Wang
Acute myeloid leukemia (AML), a common hematological cancer of myeloid lineage cells, generally exhibits poor prognosis in the clinic and demands new treatment options. Recently, direct sequencing of samples from human AMLs and pre-leukemic diseases has unveiled their mutational landscapes and significantly advanced the molecular understanding of AML pathogenesis. The newly identified recurrent mutations frequently "hit" genes encoding epigenetic modulators, a wide range of chromatin-modifying enzymes and regulatory factors involved in gene expression regulation, supporting aberration of chromatin structure and epigenetic modification as a main oncogenic mechanism and cancer-initiating event...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29074105/endogenous-hydrogen-sulfide-regulates-histone-demethylase-jmjd3-mediated-inflammatory-response-in-lps-stimulated-macrophages-and-in-a-mouse-model-of-lps-induced-septic-shock
#18
Siyu Liu, Xiling Wang, Lilong Pan, Weijun Wu, Di Yang, Ming Qin, Wanwan Jia, Chenxi Xiao, Fen Long, Junbo Ge, Xinhua Liu, YiZhun Zhu
Overproduction of inflammatory mediators contributes to uncontrolled inflammation during endotoxin shock.Cystathionine-γ-lyase (CSE), an enzyme involved in hydrogen sulfide (H2S) biosynthesis, has potential anti-inflammatory activity in a variety of inflammatory diseases. Jumonji domain-containing protein 3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in macrophage activation, but its function in CSE-mediated anti-inflammatory activities remains unknown. In the present study CSE was found to be upregulated in macrophages and mouse lipopolysaccharide (LPS) challenge models...
October 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29073101/utx-guided-neural-crest-function-underlies-craniofacial-features-of-kabuki-syndrome
#19
Karl B Shpargel, Joshua Starmer, Chaochen Wang, Kai Ge, Terry Magnuson
Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D). However, the cellular and molecular etiology of histone-modifying enzymes in craniofacial disorders is unknown. We now establish Kabuki syndrome as a neurocristopathy, whereby the majority of clinical features are modeled in mice carrying neural crest (NC) deletion of UTX, including craniofacial dysmorphism, cardiac defects, and postnatal growth retardation...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29070530/the-histone-demethylase-jumonji-domain-containing-protein-3-jmjd3-regulates-fibroblast-activation-in-systemic-sclerosis
#20
Christina Bergmann, Amelie Brandt, Benita Merlevede, Ludwig Hallenberger, Clara Dees, Thomas Wohlfahrt, Sebastian Pötter, Yun Zhang, Chih-Wei Chen, Tatiana Mallano, Ruifang Liang, Rosebeth Kagwiria, Alexander Kreuter, Ioanna Pantelaki, Aline Bozec, David Abraham, Ralf Rieker, Andreas Ramming, Oliver Distler, Georg Schett, Jörg H W Distler
OBJECTIVES: Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis...
October 25, 2017: Annals of the Rheumatic Diseases
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